The main objective of this proposal is to characterize the mechanism of insulin gene transcription in pancreatic beta cells. In particular, I want to define the role of ERK (extracellular signal-regulated kinase) in this process. The specific aims of the project are: 1) to identify and characterize direct and indirect substrates of activated ERK that are linked to insulin gene transcription; 2) to determine the localization of ERK activation of specific substrates and transcription factors involved in insulin gene transcription; and 3) to characterize the effects of various stimuli (glucose, free fatty acids, insulin, cAMP). Ultimately, these studies will result in a better understanding of beta cell function and insulin signaling in relation to diabetes mellitus.